RESUMO
Objectives: EGFR-tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta-analysis aims to study the efficacy and safety of EGFR-TKI in treating patients with rmNPC. Methods: We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse reaction-related events and performed meta-analysis using Stata 14.0. Results: A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR-TKI for rmNPC was 38% (95% CI = 27%-49%), the DCR was 71% (95% CI = 61%-80%), the mPFS was 6.29 months (95% CI = 5.22-7.35), and the mOS was 15.94 months (95% CI = 14.68-17.20). The most common grade 3-4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%-61%) for grade 3-4 adverse events (AEs). The anti-PD1 combined with TKI treatment method is more effective than the EGFR-TKI alone for treating rmNPC. Conclusion: The study shows that EGFR-TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3-4 AEs. More RCT trials are needed in the future to verify the efficacy of anti-PD1 combined with TKI treatment method.
RESUMO
The widespread existence of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47) in the environment has aroused great concern. BDE-47 induces the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanism has not been fully elucidated. Here, we further investigate the underlying mechanism using BALB/c mice. After BDE-47 exposure, the livers of mice enlarged, the serum levels of ALT, ALP, TG and TC enhanced, and hepatic steatosis occurred. Transcriptome sequencing identifies 2250 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis reveals that down-regulated DEGs are mainly enriched in pathways associated with lipid metabolism, particularly in fatty acid (FA) degradation. And up-regulated DEGs are mainly enriched in pathways related to lipid and FA transport. The expression levels of AhR, Pparγ and Cd36 involved in FA uptake are up-regulated, and those of PPARα and target genes including Cpt1 and Cyp4a1 related to ß and ω-oxidation are inhibited. These results reveal BDE-47 could lead to metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting FA uptake via upregulating Cd36 and hindering oxidative utilization by downregulating PPARα.
